Transcriptomics

Dataset Information

0

Therapeutic potential of human microglial transplantation in a chimeric model of CSF1R-related leukoencephalopathy


ABSTRACT: Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a rare, autosomal dominant primary microgliopathy caused by mutations in colony-stimulating factor 1 receptor (CSF1R). CSF1R signaling is necessary for microglial differentiation and survival. As a result, ALSP patient brains have fewer microglia and exhibit an array of neuropathologies including axonal spheroids, white matter abnormalities, reactive astrocytosis, and brain calcification. To explore the therapeutic potential of transplanting healthy human microglia, we generated ‘hFIRE’ mice, a xenotolerant mouse model of ALSP that lacks murine microglia. Remarkably, transplantation of induced pluripotent stem cell (iPSC)-derived microglial progenitors enabled rapid CNS-wide microglial engraftment, restoring a homeostatic microglial gene signature and preventing diverse ALSP-related neuropathologies. To further examine a potential autologous approach, ALSP-patient derived iPSCs were CRISPR-corrected, rescuing mutation-induced deficits in microglial proliferation, enabling brain-wide microglial engraftment, and reducing pre-existing spheroid, astroglial, and calcification pathologies within just 6 weeks. Together with the accompanying study by Munro and Colleagues, these results demonstrate the utility of FIRE mice to model diverse ALSP neuropathologies and provide initial evidence that iPSC-microglia could be further developed as a promising new therapeutic strategy for ALSP and perhaps other microglia-associated neurological disorders.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE253623 | GEO | 2024/04/24

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2024-08-29 | GSE267301 | GEO
2019-12-01 | GSE133773 | GEO
2020-05-09 | GSE150169 | GEO
2018-06-07 | GSE107635 | GEO
2024-10-06 | GSE278897 | GEO
2022-04-27 | GSE192600 | GEO
2022-04-27 | GSE192601 | GEO
2021-11-24 | GSE189033 | GEO
2022-12-21 | GSE220213 | GEO
2015-04-20 | E-GEOD-61499 | biostudies-arrayexpress